Celiac disease, also known as celiac sprue, gluten-sensitive enteropathy, or gluten intolerance is one of the most frequent food intolerances worldwide, with highest prevalence in Europe, North and South America, and Australia. Celiac disease is an inflammatory disease of the upper small intestine in genetically predisposed persons triggered by the ingestion of wheat, barley, rye and their cross-related varieties leading to a mal-absorption syndrome.
Gluten is a common dietary protein present in wheat, barley, rye and their cross-related varieties. Gluten is a complex mixture of glutamine- and proline-rich glutenin and prolamine molecules, which is thought to be the responsible factor for celiac disease induction in sensitive human individuals.
Ingestion of such proteins by sensitive individuals produces flattening of the normally luxurious, rug-like, epithelial lining of the small intestine known to be responsible for efficient and extensive terminal digestion of peptides and other nutrients. Clinical symptoms of Celiac Sprue include fatigue, chronic diarrhea, mal-absorption of nutrients, weight loss, abdominal distension, anemia, as well as a substantially enhanced risk for the development of osteoporosis and intestinal malignancies (lymphoma and carcinoma). The disease has an incidence of approximately 1 in 200 in European and North American populations.
There is some discrepancy about who/when people develop gluten intolerance. Some medical authorities claim there are two peak periods during which onset takes place. The first being infancy, between six months to two years of age, and the second being between the ages of thirty and fifty years. Women are more prone to gluten intolerance than men.
The current essential treatment of gluten intolerance is a permanent strict withdrawal of gluten form the diet. It is however important to define two categories of gluten intolerance in order to understand how the illness is affected by enzyme action in the gut. Celiac sprue is an autoimmune condition, a genetic inflammatory disorder of the small intestine. When gluten proteins break down during digestion, they fragment. These protein fragments are called peptides. In celiac sufferers, an inappropriate immune system response in the small intestine is initiated by one type of peptide, and the intestinal cells are damaged.
A second type of gluten intolerance results when the gut is injured by something other than celiac disease—the negative effect of a bacteria or yeast infection, for example, resulting in the loss of the intestinal enzymes which in turn leads to poor gluten digestion. While supplementing individuals with enzymes may be beneficial to celiac sufferers, they must remain on a strictly gluten free diet because of the possible strength of the reaction.
Using specific enzymes as supplement can be effective in minimizing the need for a gluten-free diet for those individuals at risk of developing gluten intolerance, or wherein gluten intolerance is due to gut injury.
The use of exogenous proteolytic enzymes for gluten detoxification is one of the most promising strategies for celiac disease treatment. Such enzymes have been used in both pretreatment of gluten containing flours, and as supplements. Prolyl-endoproteases are known gluten-digesting enzymes which have been shown to digest gliadin peptides.
WO 02/45524 and WO 02/46381 both disclose a proline specific endoprotease, and the use of said proline specific endoprotease for hydrolyzing proline rich peptides.
WO2013/083338 discloses recently identified specific proteolytic enzymes isolated from an Actinoallomurus strain which can be used in food processing to hydrolyze gluten.
However, the kinetics of the above referenced enzymes is not optimal when used as a supplement leading to a need to largely overdose the enzyme ingested by an individual in order to guarantee a timely digestion of the gluten, and to limit gluten exposure in the gastrointestinal tract.
It would be desirable to provide a safe an effective way to maintain or enhance gastrointestinal comfort in gluten sensitive individuals, or for delaying the onset of gastrointestinal discomfort in celiac or non-celiac gluten sensitive individuals, as well as for decreasing gluten exposure in a healthy individual.